Comparative morphological and immunohistochemical study of human meningioma after intracranial transplantation into nude mice

Abstract

Although surgical resection of benign human meningiomas is the primary goal, in case of relapse or when they are not fully resectable, other strategies including chemotherapeutical treatment would be appropriate. The initial evaluation of chemotherapeutical agents requires an appropriate tumor model, where the natural characteristics of the original benign tumor is reflected. We here tested, whether primary cell cultures of benign human meningiomas would reliably grow after intracranial transplantation into mice, and whether they would show histomorphological and immunohistochemical characteristics of the original human tumor. Cells of 11 benign human meningiomas were transplanted into the prefrontal cortex of nude mice. After 3 months, the mice were sacrificed and their brains were histologically processed for morphological characterization and measurement of tumor volume. Additionally, the proliferation index (PI), the microvessel density, and epithelial membrane antigen (EMA) were compared between human meningiomas and tumors grown in mice by using immunohistochemical methods. Further, cyclooxygenase-2 (COX-2) expression, a possible target for pharmacological manipulation, was examined. The results showed in almost all mice (93%) a tumor formation with meningothelial histomorphology comparable to the original human tumors. The PI, vascular density and COX-2 expression were similar between human and mice meningiomas, but EMA expression was reduced in mice (P<0.01). In conclusion an implantation of benign human meningioma primary cell cultures in mice reliably results in tumor formation with morphological and immunohistological features comparable to the original human tumor. This model may therefore be suitable to test novel therapeutic agents.